EFFICIENCY COMPARISON
    33%
    53%
    RRMS
    SPMS
    At the follow-up of 33.6 months
    (MIST, Phase III, Randomized, n=55)
    At the follow-up of 48 months
    (Mitoxantrone, ASTIMS, n=12)
    INTERNATIONAL EXPERIENCE
    SURVIVAL
    TIME
    RELAPSE free

    EFFECTIVENESS
    OF
    DISEASE MODIFIED THERAPY

    PROGRESSIVE free
    94%
    87%
    RRMS
    SPMS
    At the follow-up of 36 months
    (AHSCT RUSSIA, n=258)
    At the follow-up of 36 months
    (AHSCT RUSSIA, n=160)
    Pirogov National Center Experience
    SURVIVAL
    TIME
    RELAPSE free

    EFFECTIVENESS
    OF
    HDIT with AHSCT

    PROGRESSIVE free
    Our experience
    Effectiveness of HDIT with AHSCT at the follow-up
    NEDA under different treatment strategies in patients with RRMS
    Proportion of patients maintaining no evidence of disease activity (NEDA) status over time under different treatment strategies.

    Points connected by a line represent longitudinal observations in the same study
    CLIMB = Harvard Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) study
    DMT = Drug-Modifying Therapy
    HSCT = Hematopoietic Stem Cell Transplantation
    MIST = Multiple Sclerosis International Stem Cell Transplant Trial
    (Copyright permission from: Burt RK, Tappenden P, Han X, Quigley K, Arnautovic I, Sharrack B, Snowden JA, Hartung D. Health economics and patient outcomes of hematopoietic stem cell transplantation versus disease-modifying therapies for relapsing-remitting multiple sclerosis in the United States of America. Mult Scler Relat Disord. 2020;45:102404.)
    Autologous HSCT for Relapsing-Remitting Multiple Sclerosis
    Three examples of different myeloablative BEAM/ATG (carmustine (BCNU), etoposide (ETP), cytosine arabinoside (Ara-C), melphalan/anti-thymocyte globulin) conditioning regimens for relapsing-remitting multiple sclerosis.

    Refer to details in each hematopoietic stem cell transplantation publication, as these are 3 examples and not all the variations in BEAM/ATG and G-CSF dosing strategies.

    (A) BEAM/ATG over 7 days
    (B) BEAM/ATG over 6 days
    (C) less intense mini-BEAM

    ATGAM = anti thymocyte gamma globulin (equine origin)
    rATG = rabbit origin anti-thymocyte globulin
    G-CSF = granulocyte colony stimulating factor
    HSC = hematopoietic stem cell.
    Common non-myeloablative regimens for RRMS

    A - cyclophosphamide/antithymocyte globulin
    B - cyclophosphamide/rituximab (verbal communication Dr. Federenko, Moscow, Russia)
    C - split dose cyclophosphamide/ rituximab

    G-CSF = granulocyte colony-stimulating factor,
    HSC = hematopoietic stem cell,
    rATG = rabbit anti-thymocyte globulin.

    Uppsala (Uppsala, Sweden) and the other from Northwestern University (Chicago, US).
    Both studies demonstrated dramatic improvements in neurologic disability of a magnitude that had never previously been reported in clinical trials with DMTs.

    Since then several studies of HSCT performed predominately or solely for RRMS have been published with similar results (Table 41.1).

    To better understand the profound effect of HSCT for MS, the data were collected before some of the highly active DMTs were licensed, and being a real world setting, a percentage of patients could have been off treatment for variable periods of time.

    In comparison, after HSCT for RRMS, NEDA is roughly 70-90% at 2 years and 68-80% at 5 years

    NEDA, while a useful clinical endpoint, does not capture improvement in neurologic disability that is most often measured
    Indications and Efficacy
    of Disease-Modifying Therapies and Supportive Care of Multiple Sclerosis
    Indications and Efficacy of DMTs* - International Experience